Abstract
The potencies in producing muscle relaxation, and in antagonizing apomorphine-induced climbing and hypothermia in mice, were examined for chlorpromazine, levomepromazine and their main metabolites, and for fluphenazine and 7-hydroxy fluphenazine. 3-Hydroxy chlorpromazine was more potent than chlorpromazine in antagonizing apomorphine-induced climbing, while levomepromazine and 3-hydroxy levomepromazine were equipotent in this test. The 3-hydroxy metabolites of chlorpromazine and levomepromazine were more potent than the parent compounds in antagonizing hypothermia, and had significantly weaker muscle relaxant effects than the parent compounds. The 7-hydroxy and N-monodesmethyl metabolites were generally less potent than the parent compounds in antagonizing apomorphine-induced effects. N-Monodesmethyl levomepromazine had a pronounced muscle relaxant effect, like levomepromazine itself. The sulphoxide metabolites of chlorpromazine and levomepromazine were inactive in all tests. Their potencies in these tests indicate that among the metabolites 7-hydroxy chlorpromazine, N-monodesmethyl chlorpromazine and 3-hydroxy levomepromazine, which have all been identified in plasma from patients, may contribute to the antipsychotic effects of the drugs, and furthermore that N-monodesmethyl levomepromazine may contribute to the sedative effects of levomepromazine.
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Morel, E., Lloyd, K.G. & Dahl, S.G. Anti-apomorphine effects of phenothiazine drug metabolites. Psychopharmacology 92, 68–72 (1987). https://doi.org/10.1007/BF00215481
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DOI: https://doi.org/10.1007/BF00215481